INVEGA (Extended-Release Tablets) is indicated for:

Schizophrenia: (adults and adolescents 12-17 years of age)

• The efficacy of INVEGA in schizophrenia was established in three 6-week trials in adults and one 6-week trial in adolescents, as well as one maintenance trial in adults.

Schizoaffective Disorder: (adults)

• For the treatment of schizoaffective disorder as monotherapy and an adjunct to mood stabilizers and/or antidepressant therapy.

The efficacy of INVEGA in schizoaffective disorder was established in two 6-week trials in adults.

Concomitant use of INVEGA with risperidone has not been studied. Since paliperidone is the major active metabolite of risperidone, consideration should be given to the additive paliperidone exposure if risperidone is coadministered with INVEGA.

INVEGA SUSTENNA (Extended-Release Injectable) is indicated for:

Schizophrenia in Adults

Schizoaffective Disorder in Adults as Monotherapy and as an Adjunct to Mood Stabilizers or Antidepressants

Since paliperidone is the major active metabolite of risperidone, caution should be exercised when INVEGA SUSTENNA is co-administered with risperidone or with oral paliperidone for extended periods of time. Safety data involving concomitant use of INVEGA SUSTENNA with other antipsychotics is limited.

INVEGA SUSTENNA is intended for intramuscular use only. Do not administer by any other route.

Renal Impairment: As INVEGA has not been studied in patients with creatinine clearance below 10 mL/min, use is not recommended in such patients. INVEGA SUSTENNA has not been systematically studied in patients with renal impairment. INVEGA SUSTENNA is not recommended in patients with moderate or severe renal impairment (creatinine clearance < 50 mL/min).

INVEGA and INVEGA SUSTENNA have not been studied in patients with severe hepatic impairment.

Because the INVEGA tablet is non-deformable and does not appreciably change in shape in the gastrointestinal tract, INVEGA should ordinarily not be administered to patients with pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic, for example: esophageal motility disorders, small bowel inflammatory disease, “short gut” syndrome due to adhesions or decreased transit time, past history of peritonitis, cystic fibrosis, chronic intestinal pseudo obstruction, or Meckel’s diverticulum).

Because INVEGA SUSTENNA has the potential for inducing orthostatic hypotension, an additive effect may occur when INVEGA SUSTENNA is administered with other therapeutic agents that have this potential including nitrates, antihypertensive medicines, thiazide diuretics, beta blockers (e.g. acebutolol), angiotensin-converting enzyme (ACE) inhibitors (e.g. lisinopril), angiotensin II receptor blockers (ARBs) (e.g. candesartan), calcium channel blockers(e.g. amlodipine), alpha-blockers (e.g. prazosin), alpha-agonists (e.g. clonidine), other diuretics (e.g. loop, K-sparing), vasodilators (e.g. hydralazine).

Patients with Parkinson’s Disease or Dementia with Lewy Bodies can experience increased sensitivity to INVEGA SUSTENNA.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. INVEGA and INVEGA SUSTENNA is not approved for use in patients with dementia-related psychosis.

Leukopenia/neutropenia have been reported. Agranulocytosis has also been reported.

Paliperidone causes a modest increase in the corrected QT (QTc) interval. Certain circumstances may increase the risk of the occurrence of Torsades de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including (1) bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval.

Somnolence, postural hypotension, motor and sensory instability have been reported with the use of antipsychotics, including INVEGA and INVEGA SUSTENNA which may lead to falls and, consequently, fractures or other fall-related injuries. For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs, including paliperidone.

Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to predict which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.

The risk of developing tardive dyskinesia and the likelihood that it will become irreversible appear to increase with duration of treatment and the cumulative dose. The syndrome can develop after relatively brief treatment periods, even at low doses. It may also occur after discontinuation of treatment.

Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue.

Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in patients with advanced Alzheimer’s dementia.

Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain.

Hyperglycemia and diabetes mellitus, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have been reported in patients treated with all atypical antipsychotics.

Drugs with alpha-adrenergic blocking effects have been reported to induce priapism.

Like other antipsychotic drugs, INVEGA and INVEGA SUSTENNA should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold. Conditions that lower the seizure threshold may be more prevalent in patients 65 years or older.

In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly subjects with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks) including fatalities compared to placebo-treated subjects.

Antipsychotics, including INVEGA  have the potential to impair judgment, thinking, or motor skills. Patients should be cautioned about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that paliperidone therapy does not adversely affect them.

Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects.

Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents.

Paliperidone can induce orthostatic hypotension and syncope in some patients because of its alpha-adrenergic blocking activity.

The use of paliperidone should be avoided in combination with other drugs that are known to prolong QTc including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval. Paliperidone should also be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias.

Avoid using a strong inducer of CYP3A4 and/or P-gp (e.g., carbamazepine, rifampin, St John’s Wort) during the 1-month dosing interval for INVEGA SUSTENNA, if possible. If administering a strong inducer is necessary, consider managing the patient using paliperidone extended release tablets.

Like other drugs that antagonize dopamine D2 receptors, paliperidone elevates prolactin levels and the elevation persists during chronic administration.

Paliperidone may antagonize the effect of levodopa and other dopamine agonist.

Use of first generation antipsychotic drugs during the last trimester of pregnancy has been associated with extrapyramidal symptoms in the neonate.

Paliperidone is excreted in human breast milk.

GoToSource (extended-release tablets)
GoToSource  (extended-release injectable)

• Use in patients under 18 years of age for schizoaffective disorder. GoToSource

• Use in patients under 12 years of age for schizophrenia. GoToSource

• Dementia-related psychosis. GoToSource

• Obsessive-compulsive disorder. GoToSource

• Autism. GoToSource

• Bipolar disorder and acute mania. GoToSource

• Asperger syndrome. GoToSource

• Attention-deficit/hyperactivity disorder. GoToSource

• Post-traumatic stress disorder. GoToSource

Death of elderly patients with dementia-related psychosis. GoToSource

Leukopenia and neutropenia (lowered white blood cell count). GoToSource

Priapism (persistent and painful erection). GoToSource

Raised cholesterol and triglycerides, drooling, hypertonia (abnormal increase in muscle tension) worsening of schizophrenia and psychotic disorders. GoToSource

Postural hypotension, cardiac arrhythmia, sudden cardiac death, obesity and type 2 diabetes mellitus. GoToSource

Sedation and hyperprolactinemia (high levels of prolactin). GoToSource

Convulsions, edema, dysarthria (motor speech disorder) and transient ischemic attack. GoToSource

Neuroleptic malignant syndrome (life-threatening neurological disorder). GoToSource

Tardive dyskinesia (involuntary movements). GoToSource

Rhabdomyolysis (breakdown of muscle tissue). GoToSource

Urinary incontinence. GoToSource

Disruption of menstrual cycle, lactation in women, breast swelling, sexual dysfunction, akathisia and decreased bone density. GoToSource

Dysphagia (difficulty in swallowing). GoToSource

Lawsuits filed for pancreatitis, diabetes, stroke, sudden death, rhabdomyolysis and gynecomastia.